Triazapentadienes as acaricides and insecticides

ABSTRACT

The preparation of triazapentadienes with acaricidal and insecticidal properties is described.

BACKGROUND OF THE INVENTION

All stages in the life cycle of ticks tend to damage the skins ofafflicted animals and thereby spoil the state of the skins with theconsequence that cattle hides and sheep skins intended for themanufacture of leather and sheep skin are reduced in quality.Furthermore, the ticks may facilitate the transmission of disease to theafflicted animal, and the general state of health and the quality offlesh of the animal may be detrimentally affected.

Belgian Pat. No. 816,760 describes a number of triazapentadienes asbroad spectrum parasiticides. It is of importance to extend this seriesof compounds to include those that are useful for protecting plants fromplant acarids such as phytophagous spider mites and plant insects suchas pea aphids (hemiptera). Activity against the yellow fever mosquito(diptera) is very much desired.

SUMMARY OF THE INVENTION

This invention is concerned with the preparation of triazapentadienes ofthe formula: ##STR1## wherein

R¹ is alkyl of 1 to 4 carbon atoms;

R² is hydrogen, halogen or alkyl of 1 to 4 carbon atoms;

R³ is cycloalkyl of 4 to 10 carbon atoms or cycloalkyl substituted byhalogen or alkyl of 1 to 4 carbon atoms; alkyl of 1 to 4 carbon atomssubstituted by phenyl or substituted phenyl; or alkyl of 1 to 4 carbonatoms substituted by cycloalkyl of 4 to 10 carbon atoms or cycloalkylsubstituted by halogen or alkyl of 1 to 4 carbon atoms; and

R⁴ is hydrogen, alkyl of 1 to 4 carbon atoms or a group --SR⁵ where R⁵is hydrogen or alkyl of 1 to 4 carbon atoms; and the acid addition saltsthereof.

DETAILED DESCRIPTION OF THE INVENTION

In this specification the term halogen means fluorine, chlorine,bromine, or iodine.

Alkyl groups containing three or more carbon atoms may be straight orbranched chain. The preferred alkyl groups contain 1 or 2 carbon atoms.

Aryl as used herein includes substituted and unsubstituted aryl groups,e.g. phenyl groups optionally substituted by C₁ - C₄ alkyl, C₁ - C₄alkoxy, halogen, trifluoromethyl, cyano, hydroxy, or an ester group ofthe formula --COOR⁶ wherein R⁶ is a C₁ - C₄ alkyl group. The preferredaryl group is a phenyl group substituted by one or two C₁ - C₄ alkyl orC₁ - C₄ alkoxy groups.

Preferred cycloalkyl groups are unsubstituted and contain 5, 6 or 7,most preferably 5 or 6, carbon atoms in the ring.

R¹ is preferably a methyl group.

R² is preferably a methyl group or a chlorine atom.

R³ is preferably an unsubstituted cyclopentyl or cyclohexyl group; amethyl or ethyl group substituted by a phenyl group, said phenyl groupbeing optionally substituted by one or two C₁ - C₄ alkyl or alkoxygroups; or a methyl or ethyl group substituted by an unsubstitutedcyclopentyl or cyclohexyl group.

In one aspect R⁴ is preferably a hydrogen atom. In another aspect R⁴ ispreferably a methyl or ethyl group, or a group of the formula --SR⁵wherein R⁵ is a methyl or ethyl group.

Suitable acid addition salts include salts with weak dibasic organicacids, e.g. maleic, citraconic, tartaric or di-p-tolyl tartaric acid.

Particularly preferred individual compounds are the following:

1-cyclohexyl-5-(2,4-dimethylphenyl)-3-methyl-1,3,5-triazapenta-1,4-diene;

1-cyclopentyl-5-(2,4-dimethylphenyl)-3-methyl-1,3,5-triazapenta-1,4-diene;

1-cyclohexyl-5-(4-chloro-2-methylphenyl)-3-methyl-1,3,5-triazapenta-1,4-diene;

1-(2-{p-tolyl}ethyl)-5-(2,4-dimethylphenyl)-3-methyl-1,3,5-triazapenta-1,4-diene;

1-(2-{3,4-dimethoxyphenyl}ethyl)-5-(4-chloro-2-methylphenyl)-3-methyl-1,3,5-triazapenta-1,4-diene;

1-(cyclohexylmethyl)-5-(4-chloro-2-methylphenyl)-3-methyl-1,3,5-triazapenta-1,4-diene;

1-(cyclohexylmethyl)-5-(2,4-dimethylphenyl)-3-methyl-1,3,5-triazapenta-1,4-diene;

1-phenethyl-5-(4-chloro-2-methylphenyl)-3-methyl-1,3,5-triazapenta-1,4-diene;

1-(2-{3,4-dimethoxyphenyl}ethyl)-5-(2,4-dimethylphenyl)-3-methyl-1,3,5-triazapenta-1,4-diene;

1-phenethyl-5-(2,4-dimethylphenyl)-3-methyl-1,3,5-triazapenta-1,4-diene;

1-cyclohexyl-5-(2,4-dimethylphenyl)-2,3-dimethyl-1,3,5-triazapenta-1,4-diene;

1-cyclohexyl-5-(2,4-dimethylphenyl)-2-ethyl-3-methyl-1,3,5-triazapenta-1,4-diene;and

1-cyclopentyl-5-(2,4-dimethylphenyl)-2,3-dimethyl-1,3,5-triazapenta-1,4-diene.

It should be understood that compounds of the formula (I) in which R⁴ isSH may exist predominantly in their tautomeric form, viz., ##STR2##

The compounds of the invention may be prepared via a number of routes,including the following:

1. Compounds in which R⁴ is hydrogen may be prepared by reacting aformamidine of the formula: ##STR3## with an isonitrile of the formulaR³.NC. The reaction may be effected in the presence of a suitablecatalyst, most preferably a cuprous catalyst such as cuprous oxide orcuprous chloride in a trace amount, a suitable reaction temperaturebeing 50° to 80° C. Increase reaction temperatures are not generallyrecommended because they tend to increase the formation of by-productsdue to the reaction of one molecule of compound (II) with another suchmolecule. The reaction may be effected in the presence of a suitableinert organic solvent, such as benzene or toluene.

Generally, long reaction times of at least 48 hours are necessary.

Typically the product is recovered by evaporation of the reactionmixture in vacuo to leave an oil which may, if necessary, be purified bya conventional procedure such as treatment with neutral alumina in40°-60° petroleum ether. The purified oil may crystallise on standing togive crystals of the desired product of the formula (I).

The isonitriles of the formula R³.NC and the formamidines of the formula(II) are either known compounds or may be prepared by proceduresanalogous to those of the prior art. Methods for the preparation offormamidines falling within the formula (II) are described for examplein British Patent Specifications No. 964,640, 1,039,930 and 1,327,936.

2. a. Compounds in which R⁴ is a hydrogen atom or a lower alkyl groupmay be prepared by reacting a formamidine of the formula: ##STR4## withan imidate of the formula: ##STR5## wherein R⁷ is a C₁ - C₄ alkyl groupand R⁴ is as defined above in this method.

The reaction is typically carried out by heating the reactants togetherfor several hours, followed by evaporating the resulting mixture todryness, adding a suitable inert solvent such as iso-octane, filtering,purifying the filtrate by treatment with carbon and basic alumina,filtering again, adding further solvent, and finally cooling thefiltrate to e.g. -60° C to crystallise the desired product out ofsolution. The product may, if desired, be purified by recrystallisationfrom a suitable solvent.

The imidates of the formula (III) are either known compounds or may beprepared by methods analogous to those of the prior art, e.g. asfollows: ##STR6##

b. Conversely, it is also possible to prepare compounds in which R⁴ is ahydrogen atom or a lower alkyl group by reacting an imidate of theformula: ##STR7## wherein R⁷ is a C₁ -C₄ alkyl group, with an amidine ofthe formula: ##STR8##

3. Compounds of the formula (I) in which R⁴ is a hydrogen atom or a C₁ -C₄ alkyl group may be prepared by reacting an amidine of the formula:##STR9## with an isonitrile of the formula: ##STR10##

The reaction and isolation of the product may be carried out in asimilar manner to method (1) above, although in some cases it ispossible to use reaction temperatures of above 80° C withoutsubstantially increasing the formation of by-products.

The starting materials of the formula (V) may be obtained in aconventional manner, e.g. by the reaction of an imidate of the formula:

    CH.sub.3 -- N=C.(R.sup.4)(OCH.sub.3)

with an amine of the formula R³ NH₂.

4. Compounds of the formula (I) in which R⁴ is a group of the formula--SR⁵ may be prepared by reacting a formamidine of the formula:##STR11## with an isothiocyanate of the formula R³.NCS, therebyobtaining a product in which R⁵ is a hydrogen atom, followed by, ifdesired, alkylating the said product with a suitable alkylating agent toobtain a compound in which R⁵ is a C₁ - C₄ alkyl group.

The reaction between the isothiocyanate and compound (II) may be carriedout by stirring the reactants at room temperature in an inert solvent,e.g. ether, for up to 24 hours. The product may be obtained by removalof the solvent by evaporation, followed by trituration with e.g. 60°-80°petroleum ether. If desired, the product may be recrystallised from asuitable solvent, e.g. petroleum ether.

Alkylation may be carried out using a suitable alkylating agent, e.g.methyl fluorosulfonate (F.SO₂.OCH₃) or triethyloxonium fluoborate ([Et]₃O^(+BF) ₄ ⁻), in a conventional manner.

5. The salts of the compounds of the formula (I) may be made in aconventional manner, e.g. by mixing a solution of the free base in asuitable solvent, e.g. diethyl ether, with a solution of the acid in asuitable solvent, e.g. diethyl ether, and recovering the salt as aprecipitate.

The compounds of the formula (I) have acaricidal activity, particularlyagainst all stages in the life cycle, including gravid female ticks, ofthe cattle ticks Boophilus microplus, Haemaphysalis longicornus,Rhipicephalus appendiculatus and Boophilus decoloratus.

In one test, five freshly collected, fully engorged Boophilus microplusadult/female ticks are used for each acaricidal compound. Using amicro-pipette 10 micro-litres of a solution containing 10 micro-grams ofthe acaricidal compound in ethanol or acetone, is applied to the dorsalsurface of each of the ticks. The treated ticks are placed in weighed 1× 2 glass vials, weighed and stored at 26° C and 80% + R.H. in plasticboxes for two weeks. The ticks are then removed from the vials and thevials weighed to give the weight of eggs laid by the ticks. Anyreduction in the egg laying of the treated ticks is calculated as apercentage of the eggs laid by untreated control ticks.

The eggs are returned to the incubator for a further 3 weeks after whichtime the percentage of eggs hatching is estimated.

The percentage reduction in the anticipated reproduction of the ticks iscalculated using the weight of eggs laid and the percentage of eggshatching.

The test may be repeated using smaller amounts of the acaricidalcompound.

In another test, using a pipette 0.5 ml of a solution containing 0.5 mgof the acaricidal compound in ethanol or acetone is spread evenly on toa Whatman No. 1 filter paper 8 cm × 6.25 cm (50 sq. c.m.) to give adosage of 100 mg/m².

The treated paper is allowed to dry at room temperature, folded with thetreated surface inside and two short edges sealed with a crimpingmachine. The open ended envelope is placed in a 11b Kilner jarcontaining damp cotton wool in a plastic pot and stored in an incubatorat 26° C for 24 hours. 20 - 50 Boophilus microplus larvae, which hadlatched 8 - 14 days previously, are placed in the envelope using a smallspatula. The open end is then crimped to form a sealed packet. Thetreated paper containing the larvae is returned to the Kilner jar andkept for a further 48 hours in the incubator. 20 - 50 larvae are placedsimilarly in an untreated paper envelope to act as controls. At the endof the 48 hour test period the mortality is noted and recorded as apercentage after correction for any mortality among the untreatedcontrol ticks.

The test may be repeated using smaller amounts of the acaricidalcompound.

In addition to percentage effectiveness figures, ED₅₀ results can beobtained from dose response measurements using any of theafore-described tests.

Activity against Haemaphysalis longicornus nymphs may be measured in asimilar manner to the above larvae test.

The activity of the compounds of the Examples detailed hereinafteragainst the tick Boophilus microplus is set out in the following Table:

                                      TABLE                                       __________________________________________________________________________    Boophilus Microplus (in vitro)                                                       Larva (Contact)                                                                             Adult (Topical)                                                                    % Reduct'n                                                                          % Reduct'n                                    Example   Dose       Dose in egg                                                                              in egg                                        No.      (mg/m.sup.2)                                                                        % Kill                                                                              (μg/tick)                                                                       laying                                                                              hatch                                         __________________________________________________________________________    I and XVIX                                                                             100   100   10   94    100                                           (free base)                                                                            12.5  100   4    81    97                                            I (maleate                                                                             100   96    10   96    100                                           salt)                                                                         I (citra-                                                                     conate   100   100   10   97    100                                           salt)                                                                         II       100   100   10   100   100                                           III      100   100   10   77    100                                                    12.5  100   4    --    87                                            IV       100   100   10   63    86                                                     12.5  96    --   --    --                                            V        100   100   10   90    100                                                    6.25  100   4    --    85                                            VI       100   100   10   57    87                                            VII      100   100   10   88    99                                                     6.25  100   8    --    83                                            VIII     100   100   10   79    100                                                    6.25  100   8    --    90                                            IX       100   100   10   99    100                                                    12.5  86    2    --    95                                            X        100   100   10   30    84                                                     12.5  100   8    61    99                                            XI       100   100   10   100   100                                                    12.5  100   2    63    98                                            XII      100   100   10   99    100                                                    --    --    2    84    96                                            XIII     100   100   10   97    100                                           (free base)                                                                            1     100   8    --    95                                                     0.5   96    4    --    79                                            XIII     100   100   10   60    99                                            (citra-  12.5  91    8    --    85                                            conate                                                                        salt)                                                                         XIV      100   100   10   90    99                                                     1     100   8    --    98                                                     0.5   98    4    --    87                                            XV       0.25  98    10   --    100                                           XVI      100   26    10   60    96                                                     --    --    8    --    90                                            XVII     100   100   10   32    70                                                     25    98    --   --    --                                            XVIII    100   100   10   14    23                                                     50    89    --   --    --                                            __________________________________________________________________________

Thus the invention provides an acaricidal/or insecticidal compositioncomprising a compound of the formula (I) together with a diluent orcarrier. The diluent or carrier may be a solid or a liquid, optionallytogether with a dispersing agent, emulsifying agent or wetting agent.The compositions of the invention include not only compositions in asuitable form for application but concentrated primary compositionswhich may be supplied to the user and which require dilution with asuitable quantity of water or other diluent prior to application.Typical compositions of the invention include, for example, dustingpowders, dispersible powders, solutions, dispersions, emulsions andemulsifiable concentrates.

A dust may be made by mixing the appropriate amount of the finelydivided active compound with a solid pulverlent diluent or carrier suchas talc, clay, calcite, pyrophyllite, diatomaceous earth, walnut sheelflour, silica gel, hydrated alumina, or calcium silicate. As analternative method of preparation, the diluent or carrier is mixed witha solution of the active compound in a volatile organic solvent such asbenzene, the solvent being subsequently removed by evaporation.Preferably, the active compound will be present in the dust in an amountof from about 0.25 to about 4% by weight.

Dispersible powders, of special value for spray applications, may bemade by adding a suitable dispersing agent to the active compound, or toa dust containing the active compound, so that a stable aqueousdispersion of the active compound is formed on mixing the powder withwater. The dispersible powders preferably contain from about 25 to 75%by weight of the active compound.

Emulsifiable concentrates comprise a solution of the active compound ina substantially water-immiscible non-toxic organic solvent containing anemulsifying agent. Suitable solvents include, for example, toluene,xylene, petroleum oil, and alkylated naphthalenes. Preferably, theconcentrate will contain 5-75 gms. of the active compound per 100 ml. ofsolution. The concentrates may be diluted with water prior to use togive a concentration of the active compound in the aqueous medium offrom e.g. about 0.005 to about 0.1% w/v (g/100 ml.), or approximately 5to 1000 p.p.m. The volatile solvents, e.g. toluene and xylene, evaporateafter spraying to leave a deposit of the active ingredient. The made upspray or dip may be an emulsion or solution.

The compositions of the invention may be applied to ground, such as thataround dairies, in order to combat e.g. cattle ticks thereon. However,it is preferred to treat animals by spraying them or passing themthrough animal dips.

Thus the present invention also provides a method for protectinganimals, particularly cattle, from acarids, particularly cattle ticks,which comprises treating the animal externally with an acaricidal amountof a compound of the formula (I) or acaricidal composition as definedabove.

The compositions of the invention may also contain a pesticide,fungicide, additional acaricide, or the like.

The invention is illustrated by the following Examples, in which alltemperatures are given in °C. The compounds of the Examples werecharacterised by infra-red and nuclear magnetic resonance (n.m.r.)spectra, thin layer chromatography, and, in most cases, by meltingpoint, analytical and mass spectral data. In the n.m.r. data, theprotons responsible for the signals are underlined, s, q, t and mindicating, respectively, a singlet, quartet, triplet or multiplet.

EXAMPLE 1 ##STR12##

A mixture of N-2, 4-dimethylphenyl-N¹ -methyl formamidine (3.0 g,0.0185M), cyclohexane isonitrile (2.01 g, 0.0185M), benzene (60 ml.) andcuprous oxide (trace amount) was refluxed for 2 hours. Evolution ofmethylamine was observed and heating was immediately stopped. Thereaction was left at room temperature for nine days when analysis bythin layer chromatography (t.l.c.) indicated that a significant quantityof the amidine still remained in the reaction mixture. The mixture wasthen heated at about 70° for 8 hours, when t.l.c. analysis indicatedthat a small amount of the amidine still remained. After leavingovernight, the reaction mixture was heated at about 70° for a furthersix hours, filtered, and concentrated in vacuo to leave a deep red oil(4.7 g). The deep red oil was purified by treatment with neutral aluminain 40°-60° petroleum ether. Evaporation of the ether in vacuo affordedan almost colourless oil which crystallised on standing to yield largecolourless prisms of 1-cyclohexyl-5-(2,4-dimethylphenyl)-3-methyl-1,3,5-triazapenta-1, 4-diene, m.p. 55°-57.5°.

Analysis: Found: C, 75.60; H, 9.40; N, 15.59%. Required: C, 75.24; H,9.29; N, 15.48%. B. The monomaleate salt of the compound prepared inpart A was prepared by dissolving the said compound (2.5 g) in diethylether (50 ml.), and adding the solution to a stirred solution of maleicacid (1.16 g) in diethyl ether (100 ml.). The resulting whiteprecipitate, the monomaleate salt of1-cyclohexyl5-(2,4-dimethylphenyl)-3-methyl-1,3,5-triazapenta-1,4-diene(2.6 g), had a melting point of 126.8° (decomp.) and was characterisedby n.m.r. and i.r. spectra.

C. The mono-citraconate, tartrate and di-p-tolyltartrate salts of thecompound prepared in part A above were also prepared by proceduressimilar to that described in part B. The salts were characterised bynuclear magnetic resonance and infra-red spectra, the melting point andanalytical data for the citraconate salt being as follows: m.p.128°-129°.

Analysis %: Found: C, 66.09; H, 7.82; N, 10.19; Calculated for C₁₇ H₂₅N₃.C₅ H₆ O₄ :C, 65.83; H, 7.73; N, 10.47.

In order to establish that these salts were ionic in/character and notaddition complexes, n.m.r. spectra of the free base and its salts wererun in three solvents, with and without triethylamine being added.Chloroform was used as an internal standard for the/region underinvestigation.

The shifts of the indicated protons, A and B, are shown in the followingTable. ##STR13##

                                      TABLE                                       __________________________________________________________________________                                     Di-p-tolyl                                                    Citraconate     Tartrate                                     Sample   Free Base                                                                             Salt    Tartrate Salt                                                                         Salt                                         __________________________________________________________________________    Solvent  A (δ)                                                                       B (δ)                                                                       A (δ)                                                                       B (δ)                                                                       A (δ)                                                                       B (δ)                                                                       A (δ)                                                                       B (δ)                              __________________________________________________________________________    CDCl.sub.3                                                                             7.83                                                                              7.92                                                                              8.40                                                                              9.17                                                                              --  --  --  --                                       CDCl.sub.3 + Et.sub.3 N                                                                7.75                                                                              7.85                                                                              7.72                                                                              7.80                                                                              --  --  --  --                                       DMSOd.sub.6                                                                            7.95                                                                              8.10                                                                              8.05                                                                              8.35                                                                              8.12                                                                              8.45                                                                              8.20                                                                              8.50                                     DMSOd.sub.6 + Et.sub.3 N                                                               7.90                                                                              8.05                                                                              7.92                                                                              8.02                                                                              7.91                                                                              8.03                                                                              7.92                                                                              8.01                                      HMP                                                                                            6.73                                                                              6.90                                                                              6.75                                                                              6.95                                                                              6.77                                                                              7.00                                     HMP + Et.sub.3 N                                                                       ##STR14##                                                                             ##STR15##                                                                             ##STR16##                                                                             6.64                                        __________________________________________________________________________     HMP = HEXAMETHYLPHOSPHORAMIDE.                                                DMSO = dimethylsulfoxide                                                 

No attempt was made to assign individual signals to protons A and B, butin each case the higher δ value was designated B, and the lower value A.

From the above it will be seen that there is a pronounced shift in thevalues for the indicated protons for the salt forms compared to the freebase.

A shift to a higher δ-value occurs in complexing solvents such as DMSOand HMP. The large shifts observed are caused by the protonation of theadjacent nitrogen atoms. Although a shift in the value of protons A andB does occur in complexing or hydrogen bonding solvents, this shiftincreases further on salt formation, and may be reversed by the additionof triethylamine. This indicates that the salts are ionic in characterand not simple addition complexes.

Full n.m.r. scans showed that in each case the salts were of a 1:1 ratioof base to the dibasic acid.

EXAMPLES II

The following compounds were prepared by procedures similar to that ofExample I part A, using N-(2,4-dimethylphenyl)-N¹ -methylformamidine orN-(4-chloro-2-methylphenyl)-N¹ -methylformamidine, and the appropriateisonitrile, as starting materials:

    __________________________________________________________________________     ##STR17##                                                                                                Analysis %  Molecular weights                                             M.P.                                                                              (Theoretical in brackets)                                                                 from mass spectral                    Example No.                                                                          R.sup.2                                                                              R.sup.3   ° C                                                                        C   H   N   data                                  __________________________________________________________________________    II     CH.sub.3                                                                          cyclopentyl  oil  74.70                                                                            9.10                                                                              16.25                                                                             257                                                               (74.67                                                                            9.01                                                                              16.33)                                    III    Cl  cyclohexyl   79-80°                                                                      65.79                                                                            7.60                                                                              14.27                                                                             --                                                                (65.85                                                                            7.60                                                                              14.39)                                    IV     Cl  cyclopentyl  oil  64.30                                                                            7.44                                                                              13.44                                                                             277                                                               (64.85                                                                            7.26                                                                              15.12)                                     V      CH.sub.3                                                                          ##STR18##    oil                                                                                78.26 (78.13                                                                     8.29 8.20                                                                          12.41 13.67)                                                                     307                                   VI     Cl                                                                                ##STR19##    oil                                                                                69.28 (69.60                                                                     6.68 6.76                                                                         12.81  12.82)                                                                     327                                   VII    Cl                                                                                ##STR20##    oil                                                                                64.43  (64.25                                                                    6.63 6.47                                                                         11.73  11.24)                                                                     373                                   VIII   Cl                                                                                ##STR21##    oil                                                                                67.01 (66.76                                                                     8.09 7.91                                                                         13.77  13.74)                                                                     305                                   IX     CH.sub.3                                                                          ##STR22##    oil                                                                                75.74 (75.74                                                                     9.62 9.53                                                                         14.39 14.72)                                                                      285                                   X      Cl                                                                                ##STR23##    oil                                                                                68.37 (68.89                                                                     6.48 6.42                                                                         13.19  13.39)                                                                     313                                   XI     CH.sub.3                                                                          ##STR24##    oil                                                                                71.17 (71.36                                                                     7.83 7.70                                                                         11.84  11.89)                                                                     353                                   XII     CH.sub.3                                                                         ##STR25##                                                         __________________________________________________________________________                             oil                                                                                78.10 (77.78                                                                     8.04 7.90                                                                         13.26  14.32)                                                                     293                              

EXAMPLE III

A. To a solution of methyl N-methylacetimidate (8.7 g, 0.1m) in toluene(90 ml.) was added cyclohexylamine (10.5 g, 0.105m). After 72 hours atroom temperature and 32 hours heating at 60°-70° C the solvent wasremoved by evaporation to yield an oil which crystallised on cooling.Chromatography on alumina using ether as eluent afforded N-cyclohexyl-N¹-methylacetamidine as a colourless solid (11 g), or m.p. 108.5° - 109.5°C.

Analysis: Found: C, 70.22; H, 11.92; N, 17.92%. C₉ H₁₈ N₂ requires: C,70.08; H, 11.76; N, 18.15%.

B. A solution of N-cyclohexyl-N¹ -methylacetamidine (prepared in part Aabove) (4.11g, 0.027m) and 2,4-dimethylphenyl isocyamide (3.88 g, 0.03m)in dry toluene (30 ml) in the presence of a trace amount of Cu₂ O waskept at room temperature for 150 hours, heated at 80°-85° for 14 hoursand refluxed for 21/2 hours, during which time the course of thereaction was monitored by n.m.r. spectroscopy. The resulting deep redsolution was filtered through alumina, and concentrated to yield an oil(7.5 g) which partially solidified on standing to give an oily solidwhich with scratching on a porous plate gave the required compound,1-cyclohexyl-2,3-dimethyl-5-(2,4-dimethylphenyl)-1,3,5-triazapenta-1,4-diene, m.p. 37°-39°, molecularweight from mass spectra 285.

Analysis: Found: C, 75.77; H, 9.60; N, 15.00%. Required for C₁₈ H₂₇ N₃ :C, 75.75; H, 9.54; N, 14.72%.

C. The citraconate salt of the triazapenta-1,4-diene product of part Bwas prepared by adding a solution of the citraconic acid (260 mg.,0.002m) in dry ether (10 ml) dropwise at room temperature to a solutionof the said triazapenta-1,4-diene (570 mg, 0.002m) in dry ether (10ml.). The resulting precipitate, the monocitraconate of 1-cyclohexyl-2,3-dimethyl-5-(2,4-dimethylphenyl)-1,3,5-triazapenta-1,4-diene (770 mg.),m.p. 101°-103°, was filtered off and crystallised from ethylacetate/40°-60° petroleum ether.

Analysis: Found: C, 66.34; H, 8.12; N, 9.97%. Required for C₂₃ H₃₃ N₃ O₄: C, 66.48; H, 8.01; N, 10.11%.

If desired, the triazapenta-1,4-diene free base may be liberated fromthe citraconate salt by treatment with e.g. triethylamine in ether.

EXAMPLES IV

The following compounds were prepared by the method of Example III partB, starting from the appropriate amidine and2,4-dimethylphenylisocyanide:

    __________________________________________________________________________     ##STR26##                                                                                             Analysis % or n.m.r./i.e.                                                                 Molecular weights                                            M.P. (Theoretical in brackets)                                                                 from mass spectral                       Example No.                                                                           R.sup.3                                                                             R.sup.4                                                                             (° C)                                                                       C   H   N   data                                     __________________________________________________________________________    XIV    cyclopentyl                                                                          CH.sub.3                                                                            71-73°                                                                       75.01                                                                            9.18                                                                              15.00                                                                             271                                                               (75.24                                                                            9.29                                                                              15.48)                                       XV     cyclohexyl                                                                           CH.sub.3 CH.sub.2                                                                   oil  n.m.r. (CDCl.sub.3): NCH.sub.3                                                            299                                                               τ6.65 (s,3H); CH.sub.2 CH.sub.3                                           τ7.5 (q,2H); CH.sub.2 CH.sub.3                                            τ8.9 (t,3H);                                                               ##STR27##                                                                    NCHNCH.sub.3 τ1.8                                                         (s,1H).                                                                       i.r. νCN 1600, 1620cm.sup.-.sup.1                 __________________________________________________________________________

EXAMPLE V

A mixture of N-(2,4-dimethylphenyl)-N'-methylformamidine (8.1 g, 0.05mole) and cyclohexylisothiocyanate (7.1 g, 0.05 mole) in dry ether (60ml.) was stirred at room temperature (25° C) for 18 hours. Removal ofthe solvent by evaporation, followed by trituration with petroleumether, furnished a solid,N'-(cyclohexylthiocarbamoyl)-N-(2,4-di-methylphenyl)-N'-methylformamidine,which was recrystallised from petroleum ether (b.p. 60°-80°) to give thepure product, (6.2 g), m.p. 88°. An alternative name for the product is1-cyclohexyl-5-(2,4-dimethyl)/phenyl-3-methyl-1,3,5-triazapent-4-en-2-thione.

Analysis: Found: C, 67.49; H, 8.31; N, 13.97% C₁₇ H₂₅ N₃ S requires: C,67.33; H, 8.25; N, 13.86%

EXAMPLE VI

A solution of the thiocarbamoyl formamidine prepared in Example V above(3.03 g, 0.01 mole) in dry methylene chloride (30 ml.) was treated withmethylfluorosulphonate (1 ml, 0.01 mole) and the solution was left atroom temperature for 24 hours. The resulting mixture was treated with aslight excess of triethylamine and diluted with petroleum ether (b.p.60°-80°) (100 ml.), when two layers separated. The upper layer wasseparated off and the solvent removed in vacuo to give, as a colourlessviscous oil,1-cyclohexyl-5-(2,4-dimethylphenyl)-3-methyl-2-methylthio-1,3,5-triazapenta-1,4-diene(2.45 g), molecular weight from mass spectral data 317. ##STR28##

EXAMPLE VII

A mixture of N'-(cyclohexylthiocarbamoyl)-N-(2,4-dimethylphenyl)-N'-methylformamidine (1.0 g) andtriethyloxoniumfluoborate (1.3 g) in methylene chloride (15 ml.) wasleft overnight at room temperature. The solution was then heated withexcess triethylamine and diluted with diethyl ether to precipitatetriethyl ammonium fluoborate which was filtered off. The filtrate onevaporation furnished a yellow oil which would not solidify ontrituration with ether and other solvents. The filtrate waschromatographed on a short column of silica and eluted with ethylacetate, the desired product,1-cyclohexyl-5-(2,4-dimethylphenyl)-3-methyl-2-ethylthio-1,3,5-triazapenta-1,4-diene, being in the 2nd fraction (each fraction 35ml.); molecular weight from mass spectral data 331. ##STR29##

EXAMPLE VIII

A. Formic acid (90%, 4.02 l) was added to a solution of cyclohexylamine(3 kg.) in toluene (10 l) over 2 hours during which time the temperatureincreased to 92° C. The resulting two-phase mixture was refluxed underDean-Stark conditions for 18 hours by which time water evolution hadceased. The solvent was removed by evaporation in vacuo and the product,N-cyclohexylformamide (3.837 kg.), distilled directly b.p.≈165°/18mmHg.

B. To a suspension of triethyloxonium fluoroborate (1326 g.) in ether (4l) was added N-cyclohexylformamide (806 g) over 11/2 hours under ablanket of nitrogen. After stirring for 5 hours and standing overnightthe layers were separated and the lower layer washed with ether (2 ×21). Further ether (3 l) was added followed by triethylamine untilbasic. After stirring for a further 30 minutes the solid was collectedand washed with ether. The combined filtrate and washings wereevaporated and the product, ethyl N-cyclohexylformimidate, (615 g)distilled. b.p. 85°-87°C/40 mm Hg.

C. A solution of 2,4-xylidine (3 kg.) in ether (12 l) was treated with aslow stream of hydrogen chloride until salt formation was complete. Theproduct, 2,4-xylidine hydrochloride (3.7 kg.) was collected, washed withether and dried in vacuo. To a slurry of 2,4-xylidine hydrochloride (32g) and N-methylformamide (35.4 g) in dry toluene (160 ml) was addedbenzenesulphonyl chloride (40.6 g) over 15 minutes. After stirring atambient temperature overnight water (406 ml.) was added, the layersseparated and the aqueous layer basified to pH9 with 50% aqueous causticsoda solution. The solid formed, N-methyl-N¹-(2,4-dimethylphenyl)formamidine, (31 g) was filtered, washed copiouslywith water and dried in vacuo at 50° C.

D. A mixture of N- methyl -N'-(2,4-dimethylphenyl)formamidine (20 g) andethyl N-cyclohexylformimidate (40 g) was stirred and heated at 70°-75° Cunder a pressure of 20 mm/Hg for 11/2 hours. The mixture was thenevaporated, iso-octane (400 ml.) added to the residue, and, afterstirring for 1 hour, some insoluble material removed. The filtrate wastreated with carbon ("Norit", 5g) and basic alumina (5 g), diluted withfurther iso-octane (50 ml.) and cooled to -60° C. The white crystallinesolid was rapidly filtered, washed with iso-octane (50 ml. at -60° C)and petroleum ether (b.p. 30°-40° C - 50 ml. at -60° C) and dried invacuo at 35° C. The product (30 g) was found by analysis and meltingpoint data to be identical to the product of Example 1, viz.1-cyclohexyl-5-(2,4-dimethylphenyl)-3-methyl-1,3,5-triazapenta-1,4-diene.

A suitable composition for an emulsifiable concentrate containing acompound of the invention may be as follows:

EXAMPLE IX

The constituents of an emulsifiable concentrate are as follows:

    __________________________________________________________________________    1-cyclohexyl-5-(2,4-dimethylphenyl)-3-methyl-                                                             5-75 % w/v                                        1,3,5-triazapenta-1,4-diene (product of Example I)                            Emulsifiers(s)              up to 20 % w/v                                    "Aromasol H" (mixed hydrocarbon solvent)                                                                  balance to                                                                    100 %                                             __________________________________________________________________________

The concentrate may be prepared by mixing the emulsifier(s) and solventuntil homogeneous, adding the compound prepared in Example I, andstirring until dissolution occurs.

What is claimed is:
 1. A compound of the formula: ##STR30## wherein R¹is alkyl of 1 to 4 carbon atoms;R² is hydrogen, halogen or alkyl of 1 to4 carbon atoms; R³ is cycloalkyl of 4 to 10 carbon atoms, or cycloalkylsubstituted by halogen or alkyl of 1 to 4 carbon atoms; alkyl of 1 to 4carbon atoms substituted by phenyl or phenyl substituted by one or twoC₁ - C₄ alkyl or C₁ - C₄ alkoxy groups; or alkyl of 1 to 4 carbon atomssubstituted by cycloalkyl of 4 to 10 carbon atoms or cycloalkylsubstituted by halogen or alkyl of 1 to 4 carbon atoms; and R⁴ ishydrogen or alkyl of 1 to 4 carbon atoms; and the pesticidallyacceptable acid addition salts thereof. 2.1-Cyclohexyl-5-(2,4-dimethylphenyl)-1,3,5-triazapenta-1,4-diene. 3.1-Cyclopentyl-5-(2,4-dimethylphenyl)-3-methyl-1,3,5-triazapenta-1,4-diene.4.1-Cyclohexyl-5-(4-chloro-2-methylphenyl)-3-methyl-1,3,5-triazapenta-1,4-diene.5.1-(2-[p-Tolyl]ethyl)-5-(2,4-dimethylphenyl)-3-methyl-1,3,5-triazapenta-1,4-diene.6.1-(2-[3,4-Dimethoxyphenyl]ethyl)-5-(4-chloro-2-methylphenyl)-3-methyl-1,3,5-triazapenta-1,4-diene.7.1-(Cyclohexylmethyl)-5-(4-chloro-2-methylphenyl)-3-methyl-1,3,5-triazapenta-1,4-diene8.1-(Cyclohexylmethyl)-5-(2,4-dimethylphenyl)-3-methyl-1,3,5-triazapenta-1,4-diene.9.1-Phenethyl-5-(4-chloro-2-methylphenyl)-3-methyl-1,3,5-triazapenta-1,4-diene.10.1-(2-[3,4-Dimethoxyphenyl]ethyl)-5-(2,4-dimethylphenyl)-3-methyl-1,3,5-triazapenta-1,4-diene.11.1-Phenethyl-5-(2,4-dimethylphenyl)-3-methyl-1,3,5-triazapenta-1,4-diene.12.1-Cyclohexyl-5-(2,4-dimethylphenyl)-2,3-dimethyl-1,3,5-triazapenta-1,4-diene.13.1-Cyclohexyl-5-(2,4-dimethylphenyl)-2-ethyl-3-methyl-1,3,5-triazapenta-1,4-diene.14.1-Cyclopentyl-5-(2,4-dimethylphenyl)-2,3-dimethyl-1,3,5-triazapenta-1,4-diene.15. An acaricidal or insecticidal composition comprising an effectiveamount of a compound of claim 1 and a diluent or carrier.
 16. A methodof combatting ectoparasites on animals which comprises contacting saidanimals with an effective amount of a compound of claim 1.